Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (2): 192-199.doi: 10.12307/2022.931
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Zhang Jian, Lin Jianping, Zhou Gang, Wang Benchao, Wu Yongchang
Received:
2021-11-18
Accepted:
2021-12-22
Online:
2023-01-18
Published:
2022-06-18
Contact:
Lin Jianping, Master’s supervisor, Chief physician, Department of Joint Surgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou 570311, Hainan Province, China
About author:
Zhang Jian, Master candidate, Physician, Department of Joint Surgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou 570311, Hainan Province, China
Supported by:
CLC Number:
Zhang Jian, Lin Jianping, Zhou Gang, Wang Benchao, Wu Yongchang. Etiological analysis of discoid meniscus based on whole exome sequencing[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(2): 192-199.
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2.4 基因检测结果 通过全外显子测序检测7例盘状半月板患者外周血样本,共检测出外显子变异位点6 943个,其中错义突变3 620个,同义突变732个,剪接位点附近的突变488个,剪接位点突变45个,外显子重复20个,外显子缺失84个,非移码突变136个,截断突变54个,延长突变5个,起始位点突变8个,各样本突变情况,见表2,突变分布情况,见图3。以OMIM疾病数据库为依据,筛选骨软骨发育相关共有突变基因6个,分别为PADI4(chr1p36.13)、FLNB(chr3p14.3)、SYNE1(chr6q25.1)、COL11A2(chr6p21.32)、COL2A1(chr12q13.11)、MYO9A(chr15q23),6个共有突变基因所含变异位点共15个,分别为PADI4[c.331(exon3)A>T、c.831+7(IVS7)C>T]、FLNB[c*164(exon47)T>G、c.7504(exon45)G>T]、SYNE1[c.13769 (exon78)A>G、c.3500(exon28)T>C、c.22915(exon126)G>A]、COL11A2[c.1818+60(IVS20)T>G、c.3960+17(IVS54)C>T]、COL2A1[c.1527+133(IVS23)G>A、c.1834-32(IVS27)C>T]、MYO9A[c.4310(exon25)C>T、c.428(exon2)C>T、c.5043-14(IVS25)T>G、c.4725(exon25)G>T],其中错义突变7个,非编码区突变4个,剪切位点突变3个,同义突变1个,致病证据为PM2+PP3的变异位点为PADI4[c.331(exon3)A>T]、FLNB[c.7504(exon45)G>T]和MYO9A [c.428(exon2)C>T],致病证据为PM2的变异位点为FLNB[c.*164(exon47)T>G]、COL11A2[c.1818+60(IVS20)T>G、c.3960+17(IVS54)C>T],致病证据为PP3的变异位点为SYNE1[c.13769(exon78)A>G]和MYO9A[c.4310(exon25)C>T],各变异位点详情,见表3。根据dbSNP、千人基因组、EXAC、genomeAD数据库对所筛选出的17个变异位点的发生频率进行检索,发现上述变异位点在目前已报道的人群中携带频率均较低,在东亚人群中的发生率较高的变异位点为SYNE1[c.13769(exon78)A>G]、MYO9A[c.4310(exon25)C>T、c.5043-14(IVS25)T>G],以上3个位点在EXAC(EA)中的频率分别为0.004 3,0.004 4,0.004 7,而位于FLNB基因的频率则在各个数据库中均未报道,变异频率,见表4。针对所筛选的错义突变变异位点进行蛋白质有害性预测及有害性分析,在多个蛋白质预测分析软件中均提示有害的变异位点为PADI4:c.331(exon3)A>T、FLNB:c.7504(exon45)G>T、MYO9A:c.428(exon2)C>T,其上述位点蛋白质危害性评分提示危害性较大,见表5。结合全外显子测序和生物信息学分析结果,选取PADI4(c.331A>T),FLNB(c.7504G>T),SYNE1(c.13769A>G,c.3500T>C,c.22915G>A),MYO9A(c.4310C>T,c.428C>T)分别进行验证,其中SYNE1(c.13769A>G)验证结果见图4。"
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